An Open-label Multicenter Randomized Trial to Evaluate the Efficacy of Bioven, Manufactured by Biopharma Plasma, LLC, in Complex Therapy of Patients With Pneumonia Induced by COVID-19 / SARS-CoV-2
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 9
- 主要终点
- O2 saturation (SPO2 percentage), with self-breathing
研究概览
简要总结
Pneumonia caused by coronavirus infection COVID-19 is characterized by a combination of several dangerous factors that consistently worsen the patient's condition: viral lung damage early in the disease; a sharp increase in inflammation on the background of an unbalanced immune response ("cytokine storm"); joining a bacterial infection.
The condition of patients deteriorates significantly mostly at cytokine storm development. The damaging of a large volume of lung tissue leads to develops of respiratory failure, respiratory distress syndrome, or shock. Ventilatory support becomes ineffective and patients die.
There are reports of the effectiveness of Human Normal Immunoglobulin for Intravenous Administration (IVIG) high doses when used as part of complex therapy in patients with pneumonia caused by coronavirus COVID-19. In particular, IVIG has a positive effect on survival rates, overall disease course, duration of stay in the intensive care unit, and ventilatory support duration.
The probable mechanism of action of high-dose IVIG therapy is considered to be a regulatory effect on the immune system. Similar is the known and confirmed effectiveness of IVIG for autoimmune diseases (Kavasaky disease, Guillain Barre syndrome, Chronic inflammatory demyelinating polyradiculoneuropathy, Multifocal motor neuropathy).
This trial to assesses the Efficacy of IVIG (medication trade name - Bioven, manufactured by Biopharma Plasma LLC) in the High Immunomodulatory Dose in Complex Treatment of Severe Pneumonia Caused by COVID-19 / SARS-CoV-2
详细描述
The screening stage:
The patient or his legal representative must sign an informed consent. After signing the informed consent, the screening tests&procedures are performed and the compliance with the inclusion / non-inclusion criteria is assessed.
For patients who have been screened and meet the inclusion criteria and do not fall under the exclusion criteria, a blinded randomization procedure is provided.
Randomization is performed by the IVRS method, according to the blinded-block patient's randomization table.
The clinical stage of the trial:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 18 years of age and older;
- •COVID-19 documentary confirmed by PCR lab test;
- •severe pneumonia caused by COVID-19 according to the criteria below:
- •- fever or suspicion of respiratory infection;
- •- the number of respiratory movements 30 per 1 min and above;
- •- severe respiratory failure or SpO2 <90% with spontaneous breathing indoors;
- •- the presence of foci of inflammation in the lungs according to the results of computed tomography, which is documented.
- •or if any of the conditions listed below have developed on the background of previously diagnosed coronavirus pneumonia:
- •- severe respiratory failure required mechanical ventilation (ALV);
- •- acute respiratory distress syndrome according to WHO diagnostic criteria (development within one week after the manifestation of disease clinical symptoms or emergence of new ones or deterioration of respiratory syndromes. Chest visualization (lung X-ray, CT or ultrasound); bilateral opacities not fully explaining the gravity of condition or lung collapse or nodules);
- •- sepsis according to WHO diagnostic criteria (life-threatening organ dysfunction caused by disturbance of host reaction to suspected or proven infection. The features of organ dysfunction include the following: mental change, labored or shallow breathing, low oxygenation, oliguria or anuria, rapid heart palpitation, weak pulse, cold extremities or low blood pressure, skin blotching or lab-proven coagulopathy, thrombocytopenia, acidosis, high level of lactic acid or hyperbilirubinemia);
- •- endotoxic shock according to WHO diagnostic criteria (persisting hypotension despite extensive resuscitation requiring vasoconstrictors for maintaining mean arterial pressure ≥ 65 mmHg and serum lactate level > 2 mmol/l);
- •the signed patient's informed consent to participation in the trial;
- •the negative pregnancy test (for female patients of reproductive age), readiness to use reliable contraception methods during the whole duration of the trial.
- •the ability, according to the researcher, to follow all requirements of the research protocol.
- •this study allows you to take into account the results of examinations related to the disease, conducted within 10 days before signing the Informed Consent. Such data are transferred from the primary documentation to the CRF.
排除标准
- •known intolerance to plasma or immunoglobulin drugs;
- •drug allergy or hypersensitization to immunoglobulin drugs;
- •any known counter-indication to immunoglobulin drugs according to the instruction for medical application of the tested drug;
- •pneumonia not associated with COVID-19 infection;
- •pregnancy, lactation period;
- •any clinically significant impairment of liver function (elevation of serum transaminase levels more than 3 times the upper limit of normal);
- •serum creatinine levels more than 2 times the upper limit of normal for a given age and gender;
- •established diagnosis of primary immunodeficiency;
- •verified HIV-infection;
- •immune diseases (blood immune diseases, rheumatic diseases, nephritis, etc.)
- •severe cardiovascular failure (Stage III);
- •mental illness in anamnesis;
- •the need for prescribing medicines or procedures that are incompatible with the administration of the drug within the scope of this study: monoclonal antybodies;
- •known drug addiction;
- •participation in any other clinical trial presently or within the last 30 days.
研究组 & 干预措施
Study Group (IVIG)
Patients receive IVIG (trade name - Bioven) with base therapy
干预措施: IVIG (Drug)
结局指标
主要结局
O2 saturation (SPO2 percentage), with self-breathing
时间窗: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days
The target level of SPO2 percentage - 95% and above with self-breathing, is used as one of the clinical improvement criteria
Respiratory movements rate (amount per minute), with self-breathing
时间窗: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days
The target level of respiratory movements - 28 per minute or less with self-breathing, is used as one of the clinical improvement criteria
Body temperature without antipyretics use
时间窗: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days
Measured in degrees Celsius. Fever absence (body temperature no more 37 degrees Celsius) during at least 24 hours without antipyretics, is used as one of the clinical improvement criteria.
Lymphocyte count
时间窗: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days
The target level 1000 cells / mm3 and above is used as one of the clinical improvement criteria (applicable for patients with lymphocytes count lower 1000 cells / mm3 at screening moment)
Period duration (in days) to clinical improvement
时间窗: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days
Number of days post-onset of severe pneumonia to the moment of normalization at least two from following primary outcomes: O2 saturation with self-breathing, respiratory movements rate with self-breathing, body temperature without antipyretics use, lymphocyte count (targeted levels set in the description each of these primary outcomes)
次要结局
- Time from the onset of the disease to discharge, in days(28 days)
- Duration of the need for ventilatory support, in days(28 days)
- Duration of the need for intensive care, in days(28 days)
- Duration of need for oxygenation in days (SPO2 ≤ 93% with self-breathing)(28 days)
- The C-reactive protein (CRP) level(Day 0 (screening), day 5, day 14, day 28)
- The tumor necrozis factor alpha (TNF-α) level(Day 0 (screening), day 5, day 14, day 28)
- The interleukin-1β (IL-1β) level(Day 0 (screening), day 5, day 14, day 28)
- The interleukin-6 (IL-6) level(Day 0 (screening), day 5, day 14, day 28)
- The D-dimer level(Day 0 (screening), day 5, day 14, day 28)
- The Complement (C3 component) level(Day 0 (screening), day 5, day 14, day 28)
- The Circulating immune complexes level(Day 0 (screening), day 5, day 14, day 28)
- The ferritin level(Day 0 (screening), day 5, day 14, day 28)
- The procalcitonin level(Day 0 (screening), day 5, day 14, day 28)
- IgG subtypes(Day 0 (screening), day 5, day 14, day 28)
- Survival assessment for a 28-day follow-up period since the onset of severe pneumonia(28 days)